Studies are being carried out to determine the potential influence of major histocompatibility complex (MHC) genes/gene products (HLA antigens) on disease process and outcome by determining the relative frequency of specific alleles in affected and control populations. The cohorts under study are HIV-infected homosexual men and hemophiliacs, cystic fibrosis (CF) patients with diabetes, and appropriate control populations. The HLA phenotype of individuals in these cohorts was determined by two methods: (1) serology, which identifies the products of the genes at the various loci, and (2) molecular techniques that identify the polymorphism in the genes. Reagents (primers and probes) have been assembled and polymerase chain reaction techniques developed to detect the 45 DRB1, 1 DRB3, 1DRB4, 2 DRB5, 2 DPA1, and 24 DPB2 alleles. Several new techniques have been developed and are now employed in HLA typing. They include the use of DNA single-strand conformation polymorphism and DNA homoduplex analysis to do routine typing for alleles of several loci. Techniques to obtain sufficient DNA from sera to perform HLA typing were developed. This was necessary in order to HLA type individuals in the study cohort who had died of AIDS and where serum or plasma was the only potential source of DNA. Techniques for identifying the polymorphic alleles at 2 loci that encode for proteins that transport peptides across the endoplasmic reticulum and have an obligatory function in assembly of the heterodimeric class I molecule are being developed. These techniques and reagents are being applied to determine the distribution of the alleles in HIV-1- infected population and disease associations. In a study of insulin- dependent diabetes (IDDM) in CF patients, the frequencies of the HLA-DQB alleles that confer risk for IDDM in the general population were increased, indicating that these immune response genes play a role in destruction of pancreatic beta cells in a disease (CF) where pancreatic distruction is part of the disease process.